Can crosstalk between DOR and PARP reduce oxidative stress mediated neurodegeneration?

Abstract

The progressive loss of structure and function of neurons leads to neurodegenerative processes which become the causative reason for various neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD) etc. These diseases are multifactorial in nature but they have been seen to possess similar causative agents to a certain extent. Oxidative Stress (OS) has been identified as a major stressor and a mediator in most of these diseases. OS not only leads to the generation of free radical species but if persistent, can possibly lead to lipid peroxidation, protein damage, DNA damage, and cell death. Anti-oxidants are endogenously present in our body to tackle oxygen metabolites but their levels reduce greatly under continuous OS conditions. In such a case, dietary supplements to replenish the anti-oxidant levels in our body is a good way of treatment but it is very slow and may not be as effective in chronic stress conditions. Thus, there is a need for more effective mechanisms to attenuate OS. Two such mechanisms which can be considered are the activation of Delta opioid receptor (DOR) and Inhibition of Poly (ADP-ribose)-polymerase1 (PARP1), which have been suggested to protect neurons and increase neuronal cell survivability in both in-vitro and in-vivo disease models. Various signaling pathways have been highlighted to probably play a significant role in attenuating OS by the activation of DOR. It would be an interesting topic of investigation to see if one of the probable mechanisms by which DOR attenuates OS could be by modulation of PARP through a cascade of intracellular signaling reactions.

Keywords: Attenuation; Delta opioid receptor (DOR); Neuroprotection; Oxidative stress (OS); Poly (ADP-ribose)-polymerase1 (PARP1).